Stargardt macular dystrophy and evolving therapies
| Autor: | Harry W. Flynn, Ninel Z. Gregori, Thomas A. Ciulla, Audina M. Berrocal, Rehan M. Hussain, Byron L. Lam |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Retinal degeneration medicine.medical_specialty genetic structures Genetic enhancement medicine.medical_treatment Clinical Biochemistry ABCA4 Lipofuscin Propanolamines Macular Degeneration 03 medical and health sciences 0302 clinical medicine Pharmacotherapy Ophthalmology Drug Discovery medicine Animals Humans Stargardt Disease Effective treatment Pharmacology biology business.industry Phenyl Ethers Therapies Investigational Genetic Therapy Stem-cell therapy Macular dystrophy medicine.disease eye diseases Complement Inactivating Agents 030104 developmental biology 030221 ophthalmology & optometry biology.protein ATP-Binding Cassette Transporters business Stem Cell Transplantation Visual phototransduction |
| Zdroj: | Expert Opinion on Biological Therapy. 18:1049-1059 |
| ISSN: | 1744-7682 1471-2598 |
| Popis: | Stargardt macular dystrophy (STGD1) is a hereditary retinal degeneration that lacks effective treatment options. Gene therapy, stem cell therapy, and pharmacotherapy with visual cycle modulators (VCMs) and complement inhibitors are discussed as potential treatments.Investigational therapies for STGD1 aim to reduce toxic bisretinoids and lipofuscin in the retina and retinal pigment epithelium (RPE). These agents include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Avacincaptad pegol is a C5 complement inhibitor that may reduce inflammation-related RPE damage. Animal models of STGD1 show promising data for these treatments, though proof of efficacy in humans is lacking. Fenretinide and emixustat are VCMs for dry AMD and STGD1 that failed to halt geographic atrophy progression or improve vision in trials for AMD. A1120 prevents retinol transport into RPE and may spare side effects typically seen with VCMs (nyctalopia and chromatopsia). Stem cell transplantation suggests potential biologic plausibility in a phase I/II trial. Gene therapy aims to augment the mutated ABCA4 gene, though results of a phase I/II trial are pending.Stem cell transplantation, ABCA4 gene therapy, VCMs, and complement inhibitors offer biologically plausible treatment mechanisms for treatment of STGD1. Further trials are warranted to assess efficacy and safety in humans. |
| Databáze: | OpenAIRE |
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